The protein arginine methyltransferase 5 promotes malignant phenotype of hepatocellular carcinoma cells and is associated with adverse patient outcomes after curative hepatectomy

蛋白质精氨酸甲基转移酶 5 促进肝细胞癌细胞的恶性表型,并与根治性肝切除术后患者的不良预后有关

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作者:Dai Shimizu, Mitsuro Kanda, Hiroyuki Sugimoto, Masahiro Shibata, Haruyoshi Tanaka, Hideki Takami, Naoki Iwata, Masamichi Hayashi, Chie Tanaka, Daisuke Kobayashi, Suguru Yamada, Goro Nakayama, Masahiko Koike, Michitaka Fujiwara, Tsutomu Fujii, Yasuhiro Kodera

Abstract

The prognosis of advanced hepatocellular carcinoma (HCC) is dismal. Novel molecular targets for diagnosis and therapy is urgently required. This study evaluated expression and functions of the protein arginine methyltransferase 5 (PRMT5) in HCC. Using HCC cell lines, the expression levels of PRMT5 mRNA were determined using the quantitative real-time reverse-transcription polymerase chain reaction, and the effect of a small interfering PRMT5-siRNA on cell phenotype was evaluated. Further, PRMT5 expression was determined in 144 pairs of resected liver tissues to evaluate its clinical significance. Regardless of their differentiated phenotypes, nine HCC cell lines expressed different levels of PRMT5 mRNA. Inhibition of PRMT5 expression significantly decreased the proliferation, invasion, and migration of HCC cell lines. Although the level of PRMT5 mRNA was not influenced by patient's background liver status, it was significantly higher in HCC tissues than in the corresponding noncancerous tissues. High levels of PRMT5 mRNA in HCC tissues were significantly associated with advanced disease stage and adverse prognosis. In conclusion, our results indicate that PRMT5 may act as a putative oncogene in HCC and that the levels of PRMT5 mRNA represent a promising prognostic marker and a potential target of molecular therapy for HCC.

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